PurposeImaging of the different resonances of hyperpolarized ¹²⁹Xe in the brain and lungs was performed using a 3D sampling density‐weighted MRSI technique in healthy volunteers.MethodsFour volunteers underwent dissolved‐phase hyperpolarized ¹²⁹Xe imaging in the lung with the MRSI technique, which was designed to improve the point‐spread function while preserving SNR (1799 phase‐encoding steps, 14‐s breath hold, 2.1‐cm isotropic resolution). A frequency‐tailored RF excitation pulse was implemented to reliably excite both the ¹²⁹Xe gas and dissolved phase (tissue/blood signal) with 0.1° and 10° flip angles, respectively. Images of xenon gas in the lung airspaces and xenon dissolved in lung tissue/blood were used to generate quantitative signal ratio maps. The method was also optimized and used for imaging dissolved resonances of ¹²⁹Xe in the brain in 2 additional volunteers.ResultsHigh‐quality regional spectra of hyperpolarized ¹²⁹Xe were achieved in both the lung and the brain. Ratio maps of the different xenon resonances were obtained in the lung with sufficient SNR (> 10) at both 1.5 T and 3 T, making a triple Lorentzian fit possible and enabling the measurement of relaxation times and xenon frequency shifts on a voxel‐wise basis. The imaging technique was successfully adapted for brain imaging, resulting in the first demonstration of 3D xenon brain images with a 2‐cm isotropic resolution.ConclusionDensity‐weighted MRSI is an SNR and encoding‐efficient way to image ¹²⁹Xe resonances in the lung and the brain, providing a valuable tool to quantify regional spectroscopic information.